Systematic evaluation and meta-analysis of Flunarizine Hydrochloride combined with traditional Chinese medicine decoction in the treatment of migraine headaches.

OBJECTIVES: To systematically evaluate the efficacy and superiority of Flunarizine Hydrochloride when combined with Traditional Chinese Medicine (TCM) Decoctions in treating migraine headaches. METHOD: The authors conducted a comprehensive search for clinical Randomized Controlled Trials (RCTs) investigating the combination of Flunarizine Hydrochloride with Chinese herbal decoctions in treating migraines. The databases searched included CNKI, VIP, Wanfang, PubMed, WOI, Cochrane Library, and Embase, covering the period from January 1, 2019, to November 10, 2023. Two independent researchers meticulously screened, extracted, and assessed the relevant data, employing the Revman 5.3 software for meta-analysis. RESULTS: The meta-analysis revealed that, in comparison to Flunarizine Hydrochloride used in isolation, the combination with Chinese herbal decoctions markedly enhanced the effective rate (RR = 1.26, 95 % CI [1.18, 1.34], p < 0.0001). Moreover, significant improvements were observed in the TCM symptom score (MD = 4.97, 95 % CI [-6.74, -3.19], p < 0.00001). The observation group demonstrated a statistically significant improvement in endothelin levels compared to the control group (I2 = 85 %, MD = -13.66, 95 % CI [-17.87, -9.45], p = 0.0001). The observation group showed a significant reduction in NRS scores compared to the control group, indicating better outcomes (I2 = 95 %, MD = -2.11, 95 % CI [-3.09, -1.12], p < 0.0001). The observation group was superior to the control group in terms of the reduction in the number of episodes (I2 = 63 %, MD = -1.16, 95 % CI [-1.45, -0.87], p = 0.007). CONCLUSIONS: The confluence of Flunarizine Hydrochloride with traditional Chinese medicine decoctions in treating migraine patients demonstrated substantial clinical efficacy and improvement in TCM symptom score over the use of Flunarizine Hydrochloride alone.

Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

Cardiac Arrest Due to Capecitabine Toxicosis Treated With ECMO and CRRT: A Case Report.

INTRODUCTION: This is the first report of a patient who developed cardiogenic shock after receiving oral chemotherapy with capecitabine and was treated with venoarterial extracorporeal membrane oxygenation combined with continuous renal replacement therapy. CLINICAL FINDINGS: A 58-year-old man developed an arrhythmia that rapidly progressed to cardiogenic shock and cardiac arrest after receiving oral capecitabine tablets to treat a rectal malignancy. INTERVENTIONS: The patient was treated with venoarterial extracorporeal membrane oxygenation in combination with continuous renal replacement therapy. OUTCOME: The patient made a full recovery and was discharged from the hospital. CONCLUSION: The use of comprehensive supportive treatments such as extracorporeal membrane oxygenation combined with continuous renal replacement therapy in patients with capecitabine-induced cardiac arrest can rapidly reduce drug concentrations, eliminate harmful substances, and improve the prognosis.

Prognostic Analysis of Lactic Acid Metabolism Genes in Oral Squamous Cell Carcinoma.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region. Lactic acid accumulation in the tumour microenvironment (TME) has gained attention for its dual role as an energy source for cancer cells and an activator of signalling pathways crucial to tumour progression. This study aims to reveal the impact of lactate-related genes (LRGs) on the prognosis, TME, and immune characteristics of OSCC, with the ultimate goal of developing a novel prognostic model. METHODS: Unsupervised clustering analysis of LRGs in OSCC patients from The Cancer Genome Atlas database was conducted to evaluate and compare TME, immune features, and clinical characteristics across various lactate subtypes. A refined prognostic model was developed through the application of Cox and Least absolute shrinkage and selection operator (LASSO) regression techniques. External validation sets were then utilised to improve model accuracy, along with a detailed correlation analysis of drug sensitivity. RESULTS: The Cancer Genome Atlas-OSCC patients were categorised into 4 distinct lactate subtypes based on LRGs. Notably, patients in subtype 1 and subtype 2 exhibited the least and most favourable prognoses, respectively. Subtype 1 patients showed elevated expression levels of immune checkpoint genes. Further analysis identified 1086 genes with significant expression differences between cancer and noncancer tissues, as well as between subtype 1 and subtype 2 patients. Selected genes for the prognostic model included ZNF662, CGNL1, VWCE, and ZFP42. The high-risk group defined by this model had a significantly poorer prognosis (P < .0001) and functioned as an independent prognostic factor (P < .001), accurately predicting 1-, 3-, and 5-year survival rates. Additionally, individuals in the high-risk category exhibited heightened sensitivity to chemotherapy drugs such as AZ6102 and Venetoclax. CONCLUSIONS: The predictive model based on the genes ZNF662, CGNL1, VWCE, and ZFP42 can serve as a reliable biomarker, providing accurate prognostic predictions for OSCC patients and potential opportunities for pharmaceutical interventions.

[Analysis of the effect of different facial nerve managements applied to tumor resection in the jugular foramen region].

Objective:To summarize the results of different facial nerve management modalities applied to tumor resection in the jugular foramen region. Methods:The clinical data of 54 patients with tumors in the jugular foramen region who underwent surgery from January 2015 to March 2023 were retrospectively analyzed: 18 males and 36 females; Age ranges from 21 to 67 years, with an average age of 44.4 years; and median follow-up time: 12 months. The House-Brackmann（HB） grading system was applied to assess the patients' facial nerve function before surgery, 1-2 weeks after surgery and at the final follow-up （HBⅠ-Ⅱ grade for good function）: 42 cases with preoperative HB grades Ⅰ-Ⅱ; partial facial nerve transposition（9 cases）, complete facial nerve transposition（28 cases）, and facial nerve excision and re-construction（17 cases） were used, respectively（stage Ⅰor Ⅱ）. Relevant factors affecting postoperative facial nerve function were analyzed. Results:Postoperative pathology confirmed 39 cases of paraganglioma, 9 cases of nerve sheath tumor, 3 cases of meningioma, and 1 case each of fibromucinous sarcoma, chondrosarcoma, and intravascular myofibroma. Facial nerve function after partial facial nerve transposition was HB grade Ⅰ-Ⅱ in 89%（8/9）; after complete facial nerve transposition was HB grade Ⅰ-Ⅱ in 86%（24/28） in 28 cases; after facial nerve severance and reconstruction was HB grade Ⅰ-Ⅱ in 2/7（Stage Ⅰ） and 0/3（Stage Ⅱ）, respectively. Tumor size and surgical approach were correlated with postoperative facial nerve function in patients with facial nerve transposition（P<0.05）. There was no statistically significant difference in facial nerve function after complete and partial facial nerve transposition（P>0.05）. Conclusion:Intraoperative stretching of the facial nerve may be an important factor affecting facial nerve function during surgical treatment of tumors in the jugular venous foramen region; for patients with facial nerve dissection, facial nerve reconstruction should be adopted according to the situation, aiming at the recovery of facial nerve function.

A physical fitness-evaluation system for outstanding Chinese male boxers.

Background: We sought to create a system to evaluate the physical fitness of outstanding Chinese male boxers that included an evaluation index, fitness level criteria, and modeling. This system was then used to assess athletes' physical fitness and development. Methods: Documentation, expert interviews, questionnaires, measurements, and statistical analyses were used in this study. Results: The physical fitness evaluation system included the following three components: (1) body shape indexes (n = 4) including the backhand upper arm circumference differential, finger span height, Cottrell index, and pelvic width/shoulder width × 100; (2) body function indexes (n = 4) including relative maximum anaerobic power, relative maximal oxygen uptake, and creatine kinase and testosterone concentrations; and (3) athletic quality indexes (n = 9) including the speed strength index, the backhand straight punch strength, 3-min cumulative punching force, backhand straight punch reaction time, backhand straight punch speed, 30-m sprint, 9-min double shake jump rope, 1-min double shake jump rope, and sitting forward bend tests. A five-point grading system to evaluate physical fitness was established and an evaluation model was proposed. Conclusions: The reference values were determined to be objective and effective using a back substitution process. Individual and differential assessments reflected the athletes' level of physical fitness. The critical values were established under the best and worst conditions and the optimal values were found to be valid and effective.

Regulation of ubiquitination and antiviral activity of Cactin by deubiquitinase Usp14 in Drosophila.

Cactin, a highly conserved protein, plays a crucial role in various physiological processes in eukaryotes, including innate immunity. Recently, the function of Cactin in the innate immunity of Drosophila has been explored, revealing that Cactin regulates a non-canonical signaling pathway associated with the Toll and Imd pathways via the Cactin-Deaf1 axis. In addition, Cactin exhibits specific antiviral activity against the Drosophila C virus (DCV) in Drosophila, with an unknown mechanism. During DCV infection, it has been confirmed that the protein level and antiviral activity of Cactin are regulated by ubiquitination. However, the precise ubiquitination and deubiquitination mechanisms of Cactin in Drosophila remain unexplored. In this study, we identified ubiquitin-specific protease 14 (Usp14) as a major deubiquitinase for Cactin through comprehensive deubiquitinase screening. Our results demonstrate that Usp14 interacts with the C_Cactus domain of Cactin via its USP domain. Usp14 efficiently removes K48- and K63-linked polyubiquitin chains from Cactin, thereby preventing its degradation through the ubiquitin-proteasome pathway. Usp14 significantly inhibits DCV replication in Drosophila cells by stabilizing Cactin. Moreover, Usp14-deficient fruit flies exhibit increased susceptibility to DCV infection compared to wild-type flies. Collectively, our findings reveal the regulation of ubiquitination and antiviral activity of Cactin by the deubiquitinase Usp14, providing valuable insights into the modulation of Cactin-mediated antiviral activity in Drosophila.IMPORTANCEViral infections pose a severe threat to human health, marked by high pathogenicity and mortality rates. Innate antiviral pathways, such as Toll, Imd, and JAK-STAT, are generally conserved across insects and mammals. Recently, the multi-functionality of Cactin in innate immunity has been identified in Drosophila. In addition to regulating a non-canonical signaling pathway through the Cactin-Deaf1 axis, Cactin exhibits specialized antiviral activity against the Drosophila C virus (DCV) with an unknown mechanism. A previous study emphasized the significance of the Cactin level, regulated by the ubiquitin-proteasome pathway, in modulating antiviral signaling. However, the regulatory mechanisms governing Cactin remain unexplored. In this study, we demonstrate that Usp14 stabilizes Cactin by preventing its ubiquitination and subsequent degradation. Furthermore, Usp14 plays a crucial role in regulating the antiviral function mediated by Cactin. Therefore, our findings elucidate the regulatory mechanism of Cactin in Drosophila, offering a potential target for the prevention and treatment of viral infections.

Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ETA ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half-life (t1/2 ) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET-1 concentrations were dose-proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high-fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.

Integrated microbiome and metabolome analyses reveal the effects of low pH on intestinal health and homeostasis of crayfish (Procambarus clarkii).

Low pH (LpH) poses a significant challenge to the health, immune response, and growth of aquatic animals worldwide. Crayfish (Procambarus clarkii) is a globally farmed freshwater species with a remarkable adaptability to various environmental stressors. However, the effects of LpH stress on the microbiota and host metabolism in crayfish intestines remain poorly understood. In this study, integrated analyses of antioxidant enzyme activity, histopathological damage, 16S rRNA gene sequencing, and liquid chromatography-mass spectrometry (LC-MS) were performed to investigate the physiology, histopathology, microbiota, and metabolite changes in crayfish intestines exposed to LpH treatment. The results showed that LpH stress induced obvious changes in superoxide dismutase and catalase activities and histopathological alterations in crayfish intestines. Furthermore, 16S rRNA gene sequencing analysis revealed that exposure to LpH caused significant alterations in the diversity and composition of the crayfish intestinal microbiota at the phylum and genus levels. At the genus level, 14 genera including Bacilloplasma, Citrobacter, Shewanella, Vibrio, RsaHf231, Erysipelatoclostridium, Anaerorhabdus, Dysgonomonas, Flavobacterium, Tyzzerella, Brachymonas, Muribaculaceae, Propionivibrio, and Comamonas, exhibited significant differences in their relative abundances. The LC-MS analysis revealed 859 differentially expressed metabolites in crayfish intestines in response to LpH, including 363 and 496 upregulated and downregulated metabolites, respectively. These identified metabolites exhibited significant enrichment in 24 Kyoto Encyclopedia of Genes and Genomes pathways (p < 0.05), including seven and 17 upregulated and downregulated pathways, respectively. These pathways are mainly associated with energy and amino acid metabolism. Correlation analysis revealed a strong correlation between the metabolites and intestinal microbiota of crayfish during LpH treatment. These findings suggest that LpH may induce significant oxidative stress, intestinal tissue damage, disruption of intestinal microbiota homeostasis, and alterations in the metabolism in crayfish. These findings provide valuable insights into how the microbial and metabolic processes of crayfish intestines respond to LpH stress.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management.

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

Polylactic acid microplastics have stronger positive effects on the qualitative traits of rice (Oryza sativa L.) than polyethylene microplastics: Evidence from a simulated field experiment.

Soil pollution by microplastics (MPs) from different types of agricultural films has received substantial attention due to its potential effects on crop quality. To date, the effects of different types of MPs on rice grain quality and their underlying molecular mechanisms have not been clarified. In this study, we examined the effects of polyethylene MPs (PE-MPs) and biodegradable polylactic acid MPs (PLA-MPs) on rice grain quality at the environmental level (0.5 %) and evaluated the molecular mechanism through transcriptome analysis. PE- and PLA-MPs increased the number of rice grains per plant by 19.83 % and 24.66 %, respectively, and decreased the rice empty-shell rate by 55.89 % and 26.53 %, respectively. However, PLA-MPs increased the 1000-seed weight by 11.37 %, whereas PE-MPs had no obvious impact in this respect. Furthermore, MP exposure, especially that of PE-MPs, affected the content of mineral elements, fatty acids, and amino acids of rice grains by disturbing the expression of genes related to these functions and metabolism. Our findings provide insights into the response of rice grains to the stress caused by different MPs.

Construction of the flagellin F mutant of Vibrio parahaemolyticus and its toxic effects on silver pomfret (Pampus argenteus) cells.

Vibrio parahaemolyticus causes diseases in aquatic organisms, leading to substantial financial losses to the aquaculture industry; its flagellin F (flaF) protein triggers severe inflammation in host cells. To enhance the understanding of the function of flaF in V. parahaemolyticus infection, in this study, a flaF-deficient mutant was constructed by employing two-step homologous recombination. The flaF-deficient mutant induced a significantly lower toll-like receptor 5 (TLR5) expression and apoptosis in fish intestinal epithelial cells than the wild-type V. parahaemolyticus. Furthermore, fluorescence labelling and microscopy analysis of TLR5 showed that V. parahaemolyticus and its mutant strain significantly enhanced TLR5 expression. Additionally, the findings suggest that flaF deletion did not significantly affect the expression of myeloid differentiation factor 88 (MyD88) and interleukin-8 (IL-8) induced by V.parahaemolyticus. In summary, V. parahaemolyticus induced a TLR5-dependent inflammatory response and apoptosis through MyD88, which was observed to be influenced by flaF deletion. In this study, we obtained stable mutants of V. parahaemolyticus via target gene deletion-which is a rapid and effective approach-and compared the induction of inflammatory response and apoptosis by V. parahaemolyticus and its mutant strain, providing novel perspectives for functional gene research in V. parahaemolyticus.

Identification and pathogenicity of Fusarium spp. associated with tea wilt in Zhejiang Province, China.

BACKGROUND: Tea is one of the most widely consumed beverages in the world, with significant economic and cultural value. However, tea production faces many challenges due to various biotic and abiotic stresses, among which fungal diseases are particularly devastating. RESULTS: To understand the identity and pathogenicity of isolates recovered from tea plants with symptoms of wilt, phylogenetic analyses and pathogenicity assays were conducted. Isolates were characterized to the species level by sequencing the ITS, tef-1α, tub2 and rpb2 sequences and morphology. Four Fusarium species were identified: Fusarium fujikuroi, Fusarium solani, Fusarium oxysporum, and Fusarium concentricum. The pathogenicity of the Fusarium isolates was evaluated on 1-year-old tea plants, whereby F. fujikuroi OS3 and OS4 strains were found to be the most virulent on tea. CONCLUSIONS: To the best of our knowledge, this is the first report of tea rot caused by F. fujikuroi in the world. This provides the foundation for the identification and control of wilt disease in tea plants.

Long non-coding RNAs and immune cells: Unveiling the role in viral infections.

Viral infections present significant challenges to human health, underscoring the importance of understanding the immune response for effective therapeutic strategies. Immune cell activation leads to dynamic changes in gene expression. Numerous studies have demonstrated the crucial role of long noncoding RNAs (lncRNAs) in immune activation and disease processes, including viral infections. This review provides a comprehensive overview of lncRNAs expressed in immune cells, including CD8 T cells, CD4 T cells, B cells, monocytes, macrophages, dendritic cells, and granulocytes, during both acute and chronic viral infections. LncRNA-mediated gene regulation encompasses various mechanisms, including the modulation of viral replication, the establishment of latency, activation of interferon pathways and other critical signaling pathways, regulation of immune exhaustion and aging, and control of cytokine and chemokine production, as well as the modulation of interferon-stimulated genes. By highlighting specific lncRNAs in different immune cell types, this review enhances our understanding of immune responses to viral infections from a lncRNA perspective and suggests potential avenues for exploring lncRNAs as therapeutic targets against viral diseases.

Treatment for Gorham-Stout syndrome with a combination of teriparatide and denosumab.

Gorham-Stout syndrome is an aggressive, non-hereditary, and rare disease affecting bone metabolism. Its etiology and pathogenesis remain elusive. The syndrome manifests with diverse clinical symptoms, often leading to frequent misdiagnoses and presenting challenges in treatment. In this study, we report a case of cranial and maxillary osteolysis in a 47-year-old female patient with somatic mutations in the VEGF-A, VEGF-B, and VEGF-C genes and the EPHB4 gene. After treatment with bisphosphonates, this patient still had persistent resorption of the mandible, but switching to a teriparatide and denosumab combination yielded substantial improvement. This study is the first report to show that teriparatide combined with denosumab can be used to treat Gorham-Stout syndrome.

Interplay of energy metabolism and autophagy.

Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or energy stress. Its regulation is intricately linked to cellular energy status. In this review, covering yeast, mammals, and plants, we aim to provide a comprehensive overview of the understanding of the roles and mechanisms of carbon- or glucose-deprivation related autophagy, showing how cells effectively respond to such challenges for survival. Further investigation is needed to determine the specific degraded substrates by autophagy during glucose or energy deprivation and the diverse roles and mechanisms during varying durations of energy starvation.Abbreviations: ADP: adenosine diphosphate; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD: glucose deprivation; GFP: green fluorescent protein; GTPases: guanosine triphosphatases; HK2: hexokinase 2; K phaffii: Komagataella phaffii; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein1 light chain 3; MAPK: mitogen-activated protein kinase; Mec1: mitosis entry checkpoint 1; MTOR: mechanistic target of rapamycin kinase; NAD (+): nicotinamide adenine dinucleotide; OGD: oxygen and glucose deprivation; PAS: phagophore assembly site; PCD: programmed cell death; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; S. cerevisiae: Saccharomyces cerevisiae; SIRT1: sirtuin 1; Snf1: sucrose non-fermenting 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TORC1: target of rapamycin complex 1; ULK1: unc-51 like kinase 1; Vps27: vacuolar protein sorting 27; Vps4: vacuolar protein sorting 4.

The Diagnostic Value of Circulating miR-29 Family for Digestive System Malignancies: A Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic value of circulating microRNA-29 (miR-29) in digestive system malignant neoplasms by meta-analysis. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science to collect studies, published through September 2022, on the diagnostic value of miR-29 in digestive system tumors. RESULTS: We included 7 studies in this meta-analysis, including colorectal cancer, esophageal squamous cell carcinomas, and cholangiocarcinoma. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.64 (95% CI, 0.53-0.74), 0.83 (0.60-0.94), 3.75 (1.42-9.91), 0.44 (0.31-0.61), and 8.63 (2.54-29.26), respectively. The area under the summary receiver operating characteristic curve was 0.75. The sensitivity of miR-29 derived from serum was higher than that of miR-29 derived from plasma for malignant digestive system tumors (0.71 vs 0.54; P = .04). CONCLUSION: This meta-analysis suggests that the circulating miR-29 family has good diagnostic performance for digestive system malignant tumors, with moderate sensitivity and good specificity.

Inhibition of ATM with KU-55933 Sensitizes Endometrial Cancer Cell Lines to Olaparib.

Background: Endometrial cancer (EC) is one of the most prevalent gynecologic cancers, which poses a serious threat to women's health worldwide. Olaparib, the first FDA-approved PARP inhibitor for the treatment of BRCA-mutated breast, ovarian and pancreatic cancers, triggers apoptosis of cancer cells through synthetic lethality by inhibiting PARP1/2 enzymatic activity and BRCA1/2-dependent homologous recombination (HR) repair deficiency. However, the synergistic lethal effects between Olaparib and inhibitors of other DNA damage response proteins, such as ATM, PTEN and RAD51, are still unknown. Aim: Exploring the synergistic lethal effect between Olaparib and KU-55933 on EC. Methods: The GEPIA database was used to test EC patient survival rate. CCK8 was used for cell viability assays. Western blot was used for examining gene levels. The wound healing assay was used to detect cell migration ability. Flow cytometry was used for detecting the apoptosis rate. All experimental conditions were repeated independently in triplicate and analyzed in three separate experiments. Results: In this study, we discovered that the frequency of ATM alterations in endometrial cancer reaches nearly 20% and that there is a positive correlation between ATM alterations and prognosis. Furthermore, we discovered that endometrial cells with low expression levels of ATM are sensitive to Olaparib. Treatment with KU-55933, a specific inhibitor of ATM, significantly enhanced the sensitivity of endometrial cancer cells to Olaparib, as evidenced by colony formation, cell migration and apoptosis assay. Further analysis revealed that KU-55933 potentiates Olaparib-induced cell apoptosis by inhibiting ATM phosphorylation. Conclusion: Our study demonstrates that inhibiting ATM could enhance the sensitivity of endometrial cancer to Olaparib, thereby providing a potential alternative treatment for the clinical treatment of endometrial cancer.

Isolation, Behavioral Identification, and Pathogenicity Assessment of Entomopathogenic Fungi from a Forest Wood Borer.

Forest wood borers (FWB) cause severe tree damage and economic losses worldwide. The release of entomopathogenic fungi (EPF) during the FWB emergence period is considered an acceptable alternative to chemical control. However, EPF resources have been significantly less explored for FWBs, in contrast to agricultural insect pests. This paper presents a protocol for exploring EPF resources from FWBs using wild Monochamus alternatus populations as an example. In this protocol, the assignment of traps baited with M. alternatus attractants to different populations guaranteed the collection of adequate samples with natural infection symptoms, during the emergence periods of the beetle. Following finely dissecting integuments and placing them onto a selective medium, fungal species were isolated from each part of beetle bodies and identified based on both molecular and morphological traits. Several fungal species were certified as parasitic EPFs via re-infection of healthy M. alternatus with spore suspensions. Their behavioral phenotypes on M. alternatus were observed using scanning electron microscopy and further compared with those on the Coleopteran model insect Tribolium castaneum. For EPFs that present consistent parasitism phenotypes on both beetle species, evaluation of their activities on T. castaneum provided valuable information on lethality for future study on M. alternatus. This protocol helped the discovery of EPF newly reported on M. alternatus populations in China, which could be applied as an efficient approach to explore more EPF resources from other FWBs.

TOR-mediated Ypt1 phosphorylation regulates autophagy initiation complex assembly.

The regulation of autophagy initiation is a key step in autophagosome biogenesis. However, our understanding of the molecular mechanisms underlying the stepwise assembly of ATG proteins during this process remains incomplete. The Rab GTPase Ypt1/Rab1 is recognized as an essential autophagy regulator. Here, we identify Atg23 and Atg17 as binding partners of Ypt1, with their direct interaction proving crucial for the stepwise assembly of autophagy initiation complexes. Disruption of Ypt1-Atg23 binding results in significantly reduced Atg9 interactions with Atg11, Atg13, and Atg17, thus preventing the recruitment of Atg9 vesicles to the phagophore assembly site (PAS). Likewise, Ypt1-Atg17 binding contributes to the PAS recruitment of Ypt1 and Atg1. Importantly, we found that Ypt1 is phosphorylated by TOR at the Ser174 residue. Converting this residue to alanine blocks Ypt1 phosphorylation by TOR and enhances autophagy. Conversely, the Ypt1S174D phosphorylation mimic impairs both PAS recruitment and activation of Atg1, thus inhibiting subsequent autophagy. Thus, we propose TOR-mediated Ypt1 as a multifunctional assembly factor that controls autophagy initiation via its regulation of the stepwise assembly of ATG proteins.